In one aspect, this invention relates to the peptides which inhibit infectivity of DNA viruses and T. bacillus. In another aspect, this invention relates to the use of such peptides to treat infections caused by DNA viruses or T. bacillus in humans.
The earliest study on the interaction of snake venom toxins and viruses was reported by Sanders et al. In 1958 the same authors demonstrated the inhibition of Semiliki forest virus. Later in 1977 these investigators observed that the venom neurotoxin interfered with human strain of Poliomyelitis virus in Rhesus monkeys. Several investigators studied the inhibitory effects of venom toxins on various RNA viruses, to name a few; Murray encephalitis virus, Rous sarcoma and MH2 tumor viruses, Newcastle disease virus and influenza virus. However, no studies are reported on DNA viruses.
Herpes simplex viruses (HSV) type 1 and type 2 are double stranded DNA viruses. The clinical entities attributable to HSV-1 include the following: (1) Acute herpetic gingivostomatitis mostly in small children, (2) Eczema herpeticum-Kaposi's varicelliform eruption. Some times it can be fatal. (3) Keratoconjunctivitis infection of the eye, with recurrent infection, can lead to permanent opacification and blindness (4) Herpes encephalitis—carries a high mortality rate and the survivors often have residual neurological defects. (5) Herpes labilis—cold sores are most common recurrent disease in the form of oral lesions.
HSV-2 is implicated in the following: (1) Genital herpes, progenitalis, is characterized by vesiculoulcerative lesions of the penis or the cervix, vulva and vagina. (2) Neonatal herpes can be transmitted to the newborn during the birth by contact with herpetic lesions in the birth canal if the mother infected with the virus. Such transmission can produce permanent brain damage. Varicella zoster virus is a double-stranded DNA virus and it is morphologically identical with herpes simplex viruses. It is a causative agent for shingles in adults which is characterized by an inflammatory reaction of the posterior nerve roots and ganglia, accompanied by the affected sensory nerves.
Currently, there is no effective treatment against the infections caused by HSV viruses. Therefore, the synthetic active Herp has great potential as a therapeutic to treat infections caused by DNA viruses.
Currently, tuberculosis (TB) is a major global health problem and Herp is inhibitory to acid fast Tubercle bacilli. Effective treatments for TB are much sought after.
In our U.S. Pat. No. 5,648,339 we derived a DNA virus-inhibiting protein from snake venom which meets many of the above needs. We named this protein Herpoxin. However, because Herpoxin is derived from snake venom, it may not gain widespread acceptance and use. Also, because Herpoxin has a molecular weight of 13.5 kDa it cannot be easily synthesized and is somewhat limited in the ways it can be effectively administered. A synthetic peptide which mimics the properties of Herpoxin would be very desirable, and would have better capabilities for crossing the blood-brain barrier and coming into contact with pathogens in the central nervous system.